Jun 8, 2012

Ayurveda formulations validated, verified by modern biology - The Hindu

Modern pharmacology is molecule-based, and often single-molecule based. The molecule is expected to act usually on a single step in the body physiology, occasionally on a ladder of steps. However, disorders such as diabetes affect a variety of biochemical processes and thus the single-molecule approach is inadequate.

It is here that a multi-component mixture becomes useful. The million-dollar puzzle is "which components?"

Traditional medications of the Ayurvedic, Unani, Siddha, or oriental schools are invariably mixtures, extracts from plants and herbs (and occasionally animals). The approach of the traditional physician is thus qualitatively different from the molecule-wallah.

And it is here that the difference of opinion starts and stays.

Today's pharmacologist says his product is evidence-based while that of the traditional vaidya or hakim is empirical.

The latter, however, contends that his is the time-proven science that works even today. And the hapless patient is willing to try anything to getter better.

Will the twain meet? Can we take traditional medications through the rigours of modern biology and pharmacology — so that validation and verification occur?

The Chinese have taken this up on a mission mode, and happily enough the renowned medical scholar-statesman Prof. M.S. Valiathan of Manipal University has initiated such a programme on some Ayurvedic practices, by bringing together Ayurvedic schools (Kottakkal Arya Vaidyasala) and modern biologists (immunologists, geneticists, biochemists, cell biologists, material scientists and chemists) on two flagship projects.

The first is to evaluate the effects of Panchakarma on body physiology, using immunological and related methods.

While the results of this project are being compiled and evaluated, early results of a second project, done in collaboration with the renowned developmental biologist Prof. Subhash Lakhotia of Banaras Hindu University and his associates Vibha Dwivedi, and Mousami Mutsuddi, have just been published in the peer-reviewed journal PLoS ONE 7(5): e37113 doi: 10.1371/journals.pone.0037113.

This study has attempted to evaluate the effects of two Ayurvedic formulations: Amalaki Rasayana (AR) and Rasa-Sindoora (RS), on the life processes of the model animal, the common fruit fly Drosophila melanogaster.

AR is prepared from gooseberry (amla, nellikai, phylanthus emblica) in a four-step procedure. The dry Amalaki powder obtained in 3 rigorous steps is blended with honey and ghee in a well-defined and quality assured protocol, by Kottakkal. Likewise, Rasa Sindoor or RS is prepared in a 3-step process, and is made up of a highly pulverised (nano-sized) dust of mercury sulphide or cinnabar.

The protocols for making AR and RS have been standardised by the Kottakkal group of E.M. Anandan, Rajesh S. Mony, and T.S. Muraleedharan. Both AR and RS have been used as health tonics in Ayurveda.

The authors set out their basic premise in a precise, rigorous manner in the paper: "Since the Ayurvedic medicines/formulations are complex integrated derivatives involving several specific preparatory steps, studies using isolated active compounds may not really provide full insight into the efficacy or mode of action of the traditional formulations.

In order to undertake scientific investigations on action/s of Ayurvedic drugs/formulations using experimental animals, there is an urgent need to develop good model systems which can permit in depth studies on the in vivo effects and mechanisms of actions of different Ayurvedic formulations."

Why choose the fruit fly as the model? Several reasons: (1) As the name Drosophila indicates, the fruit fly loves sweets, such as AR (and hopefully RS); (2) the complete developmental cycle, genetic and physiological, is well understood; one can thus follow the effects of the formulations at each stage — larva, pupa, imago, adult insect — on the anatomy, physiology, life cycle and genetic connections, (3) their life spans are in days so that their life histories can be followed through generations quickly, and (4) Prof. Lakhotia has special expertise on the developmental biology and genetics of fruit flies. What did they find?

(1) Flies fed on small doses of AR lived longer than those that did not; life span of 40 days when fed on 0.5 per ecnt AR in the feed vs 36 (however higher doses are harmful. 1 per cent reduced the life span to 30 days.)

(2) Not only does the fly live longer on AR, it also develops sooner (the egg-larva-pupa-emergence period hastened by a few hours).

(3) They also appear to produce more eggs —fecundity rises.

(4) When fed with AR or RS, the flies are able to tolerate heat (higher temperatures) better than control flies.

(5) Finally, such supplementation also appears to allow them to tolerate starvation better, i.e. can go without food longer.

Of the two formulations, AR appears to be somewhat better in some biological effects than RS.

However, the worry that some scientists have had, namely that mercury is harmful and poisons the body, does not appear to hold here. One wonders whether the mode of preparations, generating nanoparticles of HgS, has something to do with this is not clear.

(A Chinese group has shown that cinnabar does not get converted into poisonous methyl mercury in the human gut). Also, it is not the ghee or honey, used to prepare AR or RS, which are involved in the beneficial effects. Taken by themselves, they do not show any of these effects.

Likewise, dry AR powder is not as effective as the paste made with ghee and honey.

So, the Valiathan-Kottakkal-Lakhotia trio shows the positive biological effects of AR (and RS) on the fruit fly. In doing so, the fly is a useful and acceptable model for studying the effects of a drug candidate on the body and its parts. But flies are not men, not even mice.

Should one not repeat the experiments with mice or rats as experimental mammalian models? I am sure they are on the way to do so.

Even as it is now, are there lessons that the flies teach us? Note the value of moderation. Too much of a good thing (1 per cent, not 0.5 per cent supplementation) shortens life span.

And this supplementation allows starvation tolerance — a note for hunger-strikers. But more than anything else, the trio has shown that rigorous in depth analysis using modern biological, evidence-based tools and methods can be applied to validate and verify traditional medical practices.